Method for detecting 15 photoinitiators in extracting solution

Abstract

The invention relates to the technical field of chemical analysis, in particular to a method for detecting 15 photoinitiators in an extracting solution. Comprising the following steps: S1, respectively preparing 15 photoinitiator mixed standard working solutions, a mobile phase, an SST solution, a blank solution and an STD solution for later use; s2, filtering the extracting solution, and preparing a blank extracting solution for later use; and S3, carrying out sample injection test analysis by using ultra-high performance liquid chromatography-mass spectrometry, wherein the sample injection sequence sequentially comprises a blank solution, an SST solution, a blank solution, an STD solution, a blank solution, a blank extracting solution, an extracting solution, a blank solution and an SST solution. The analysis method has good specificity and high sensitivity on determination of the 15 photoinitiators in the extracting solution, and can be used for determination of the 15 photoinitiators in the extracting solution.

Description

Technical Field

[0001] The invention relates to the technical field of chemical analysis, and in particular to a method for detecting 15 photoinitiators in an extract. Background Art

[0002] Photoinitiator residues in medical devices are an issue that requires great attention. Under certain conditions, they can migrate to the surface of the device, posing a potential threat to human health. At present, the main methods for detecting photoinitiator residues are high performance liquid chromatography (HPLC), gas chromatography-mass spectrometry (GC-MS), etc. Therefore, by adopting sensitive detection methods, strictly controlling the amount and time of use, establishing a sound quality control system, and complying with relevant laws, regulations and standards, the risk of photoinitiator residues can be effectively reduced to ensure the safety and effectiveness of medical devices.

[0003] Chinese invention patent CN102818874B discloses a method for determining 16 photoinitiators in paper printing and packaging materials. It is a method for determining the residual amount of 16 photoinitiators such as 2-hydroxy-2-methyl-1-phenylacetone, methyl benzoylformate, and benzophenone. Compared with the prior art, it has the following characteristics and advantages: high efficiency, and simultaneous analysis and determination of 16 photoinitiators within 25 minutes. The liquid-liquid distribution impurity removal method used in the sample pretreatment process can better remove ink impurities in the sample extraction solution, and has the characteristics of low cost, low consumption, high efficiency, and high sensitivity, but the detection time of this method is too long. Summary of the invention

[0004] The present invention provides a method for detecting 15 photoinitiators in an extract, comprising the following steps:

[0005] S1, prepare 15 kinds of photoinitiator mixed standard working solutions, mobile phase, SST solution, blank solution and STD solution for use;

[0006] S2, taking the extract, filtering it and preparing a blank extract for later use;

[0007] S3, use ultra performance liquid chromatography-mass spectrometry to sample and analyze the extract, before sampling and analyzing the extract, first inject the mixed standard working solution and draw a standard curve, the order of injecting the extract includes: blank solution, SST solution, blank solution, STD solution, blank solution, blank extract, extract, blank solution, SST solution.

[0008] As the experiment proceeds, the instrument may be affected by various factors, such as temperature changes, solvent volatilization, sample residues, etc. These factors may cause fluctuations in instrument performance and lead to poor signal-to-noise ratio. The applicant has found that limiting the order of extract injection to: blank solution, SST solution, blank solution, STD solution, blank solution, blank extract, extract, blank solution, SST solution can improve the signal-to-noise ratio. It may be a specific injection sequence to avoid the differences in properties of larger samples injected continuously and reduce the impact of sample residues.

[0009] The 15 photoinitiators are 2-hydroxy-2-methylpropiophenone, benzophenone, 2-methylbenzophenone, 1-hydroxycyclohexylbenzophenone, ethyl 4-(dimethylamino)benzoate, methylbenzophenone, 2,2-dimethoxy-2-phenylacetophenone, methyl o-benzoylbenzoate, 2-ethylhexyl 4-(dimethylamino)benzoate, 2-methyl-4'-(methylthio)-2-morpholinylpropiophenone, isopropylthioxanthone, 4-phenylbenzophenone, 2,4-diethylthioxan-9-one, 4,4'-bis(dimethylamino)benzophenone and 4,4'-bis(diethylamino)benzophenone.

[0010] The mixed standard working solution, SST solution and STD solution all include acetonitrile.

[0011] The mobile phase includes a mobile phase A and a mobile phase B, wherein the mobile phase A includes a formic acid aqueous solution, and the mobile phase B includes methanol.

[0012] The concentration of the formic acid aqueous solution is 0.05-0.5 wt %.

[0013] Preferably, the concentration of the formic acid aqueous solution is 0.05-0.2 wt %.

[0014] The elution procedure of the liquid chromatography includes: 0-9 min, the content of mobile phase A in the mobile phase is 40-60 wt %, 9-12 min, the content of mobile phase A in the mobile phase is 1-5 wt %, and after 12 min, the content of mobile phase A in the mobile phase is 40-60 wt %.

[0015] The research in this application found that the mobile phase includes mobile phase A and mobile phase B, the mobile phase A includes aqueous formic acid solution, the mobile phase B includes methanol, and the concentration of the aqueous formic acid solution is 0.05-0.5wt%. 15 photoinitiators can be detected simultaneously. It may be that the specific mobile phase selection and ratio match the polarity, ionic strength and viscosity of multiple photoinitiator mobile phases to achieve a balance and better separation effect.

[0016] Further research found that the elution procedure of the liquid chromatography includes: 0-9min, the content of mobile phase A in the mobile phase is 40-60wt%, 9-12min, the content of mobile phase A in the mobile phase is 1-5wt%, and after 12min, the content of mobile phase A in the mobile phase is 40-60wt%. It can be ensured that there are no other interfering adjacent peaks near the target or the separation between adjacent peaks and the target should be no less than 1.5. The similarity of the types of substances measured in this application is high, and there are many interferences between them. Through a specific liquid chromatography elution procedure combined with a specific chromatographic column, the separation and peak morphology of 15 photoinitiators can be improved. It may be that the charge state and interaction force of the solute between the stationary phase and the mobile phase are changed by the selection of the mobile phase and the ionic strength matching of the specific chromatographic column, thereby improving the separation and optimizing the peak morphology.

[0017] Preferably, the elution procedure of the liquid chromatography includes: 0-9 min, the content of mobile phase A in the mobile phase is 50-60 wt%, 9-12 min, the content of mobile phase A in the mobile phase is 1-3 wt%, after 12 min, the content of mobile phase A in the mobile phase is 50-60 wt%.

[0018] The flow rate of the ultra-high performance liquid chromatography is 0.3-0.8 mL / min, the column temperature is 30-50° C., and the analysis time is 10-20 min.

[0019] Preferably, the flow rate of the ultra-high performance liquid chromatography is 0.3-0.5 mL / min, the column temperature is 40-50° C., and the analysis time is 10-20 min.

[0020] The stationary phase of the chromatographic column used in the ultra-high performance liquid chromatography comprises C18; the inner diameter of the chromatographic column is 1-3 mm, the length is 50-150 mm, and the particle size of the stationary phase is 1-5 μm.

[0021] Preferably, the stationary phase of the chromatographic column used in the ultra-high performance liquid chromatography comprises C18; the inner diameter of the chromatographic column is 2-3 mm, the length is 50-100 mm, and the particle size of the stationary phase is 1-3 μm.

[0022] The mass spectrometer ionization method includes electrospray ionization, and the capillary positive ion voltage is 2-4 kV.

[0023] Preferably, the ionization mode of the mass spectrometer includes electrospray ionization, and the capillary positive ion voltage is 3-4 kV.

[0024] The sheath gas temperature of the mass spectrometer is 300-400° C., and the sheath gas flow rate is 10-15 L / min.

[0025] Preferably, the sheath gas temperature of the mass spectrometer is 300-400°C, and the sheath gas flow rate is 10-12 L / min.

[0026] The nebulizer gas flow rate of the mass spectrometer is 5-10 L / min, and the nebulizer pressure is 40-50 psi.

[0027] Preferably, the nebulizer gas flow rate of the mass spectrometer is 5-10 L / min, and the nebulizer pressure is 45-50 psi.

[0028] Beneficial Effects

[0029] 1. Limit the order of extract injection to: blank solution, SST solution, blank solution, STD solution, blank solution, blank extract, extract, blank solution, SST solution to improve the signal-to-noise ratio.

[0030] 2. The mobile phase includes mobile phase A and mobile phase B, wherein the mobile phase A includes aqueous formic acid solution, and the mobile phase B includes methanol. The concentration of the aqueous formic acid solution is 0.05-0.5 wt %, and 15 photoinitiators can be detected simultaneously.

[0031] 3. The elution procedure of the liquid chromatography includes: 0-9min, the content of mobile phase A in the mobile phase is 40-60wt%, 9-12min, the content of mobile phase A in the mobile phase is 1-5wt%, and after 12min, the content of mobile phase A in the mobile phase is 40-60wt%. It can be ensured that there are no other interfering adjacent peaks near the target or the separation degree between the adjacent peak and the target should not be less than 1.5.

[0032] 4. The analytical method has good specificity for the determination of 15 photoinitiators in the extract.

[0033] 5. The analytical method has good sensitivity for the determination of 15 photoinitiators in the extract. DETAILED DESCRIPTION

[0034] Example 1

[0035] S1, prepare 15 kinds of photoinitiator mixed standard working solutions (standard solution concentration 1.00 μg / mL), mobile phase, SST solution, blank solution and STD solution for use;

[0036] S2, take 5 mL of the extract (50 wt% ethanol aqueous solution to extract the packaging material sample), filter it with a 0.2 μm PTFE membrane, discard the first 2 mL of the primary filtrate, collect about 1 mL of the subsequent filtrate, and prepare another blank extract (50 wt% ethanol aqueous solution) for later use;

[0037] S3, use ultra-high performance liquid chromatography-mass spectrometry for sample injection test analysis, the injection order is: blank solution, SST solution, blank solution, STD solution, blank solution, blank extract, extract, blank solution, SST solution, and the mass spectrometry scanning results are shown in Table 2.

[0038] Preparation method of 15 kinds of photoinitiator mixed standard working solution: Pipette 100.0 μL of 15 kinds of photoinitiator mixed standard working solution into a 10 mL volumetric flask, dilute to the scale with acetonitrile, mix well, and obtain a working solution with a concentration of 1.00 μg / mL.

[0039] The blank solution was acetonitrile.

[0040] SST solution preparation method: Pipette 200.0 μL of the mixed standard working solution of 15 photoinitiators into a 10 mL volumetric flask, dilute to the scale with acetonitrile, mix well, and obtain a working solution with a concentration of 20.00 μg / L.

[0041] STD solution preparation method: Pipette 1000.0 μL of the mixed standard working solution of 15 photoinitiators into a 10 mL volumetric flask, dilute to the scale with acetonitrile, mix well, and obtain a working solution with a concentration of 100.00 μg / L.

[0042] Among them, the concentration of the mixed standard working solution of 15 photoinitiators is 100μg / mL, the solvent is acetonitrile, and the manufacturer is Anpu.

[0043] The 15 photoinitiators are shown in Table 1:

[0044] Table 1

[0045]

[0046]

[0047] The specific model of the ultra-high performance liquid chromatography-mass spectrometer is: 1290infinity IⅡ&G6470A (Agilent Technologies Co., Ltd.).

[0048] The mobile phases are mobile phase A and mobile phase B, the mobile phase A is a 0.1 wt % formic acid aqueous solution, and the mobile phase B is methanol.

[0049] The elution procedure of the liquid chromatography is as follows: 0-9 min, the content of mobile phase A in the mobile phase is 50 wt %, 9-12 min, the content of mobile phase A in the mobile phase is 2 wt %, 12-15 min, the content of mobile phase A in the mobile phase is 50 wt %.

[0050] The flow rate of the ultra-high performance liquid chromatography was 0.4 mL / min and the column temperature was 45°C.

[0051] The stationary phase of the chromatographic column used in the ultra-high performance liquid chromatography includes C18; the inner diameter of the chromatographic column is 3 mm, the length is 50 m, the particle size of the stationary phase is 2.7 μm, and the model is INFINITYLAB POROSHELL120EC C18.

[0052] The ion source of the mass spectrometer is AJS ESI, the ionization mode is electrospray ionization, and the capillary positive ion voltage is 4 kV; the sheath gas temperature of the mass spectrometer is 350° C., and the sheath gas flow rate is 11 L / min; the nebulizer gas flow rate of the mass spectrometer is 6 L / min, and the nebulizer pressure is 45 psi.

[0053] Performance testing methods and data

[0054] Table 2

[0055] Compound Name Precursor ion Product ions Frag(V) CE(V) Cell Acc(V) PIEMK 325.2 281.1 163 33 3 PIEMK 325.2 176.1 163 29 3 PI907 280.1 165.1 121 21 3 PI907 280.1 88.1 121 21 3 PIEHA 278.2 166.1 146 21 3 PIEHA 278.2 151 146 33 3 PIMMK 269.2 148.1 136 25 3 PIMMK 269.2 77 136 60 3 PIDETX 269.1 241.2 131 60 3 PIDETX 269.1 184.1 131 30 3 PIPBZ 259.1 105 121 21 3 PIPBZ 259.1 77 121 53 3 PIBDK 257.1 215 131 21 3 PIBDK 257.1 186 131 49 3 PIITX 255.1 213 146 21 3 PIITX 255.1 184 146 45 3 PIOMBB 241.1 209 62 9 3 PIOMBB 241.1 152 62 49 3 PI184 205.1 105 62 17 3 PI184 205.1 77.1 62 41 3 MBP 197.1 105 150 21 3 MBP 197.1 77 150 41 3 2-MBP 197.1 105 110 21 3 2-MBP 197.1 77 110 41 3 PIEDB 194.1 151.1 109 25 3 PIEDB 194.1 134.1 109 33 3 PIBP 183.1 105 99 16 3

[0056] 1. System suitability - The signal-to-noise ratio (S / N) of the four targets PI1173, PIMMK, PIEMK, and PIEHA in the SST solution should be no less than 10. The measured values ​​at the retention time of the target in the SST solution and the extract should not exceed the concentration of 1 / 3 of the quantitative limit. The separation between adjacent peaks without interference near the target or between adjacent peaks and the target should be no less than 1.5. The test results are shown in Table 3.

[0057] Table 3

[0058]

[0059] 2. System suitability - The signal-to-noise ratio (S / N) of the four targets PI1173, PIMMK, PIEMK, and PIEHA in the STD solution should be no less than 10. The measured values ​​at the retention time of the target in the STD solution and the extract should not exceed the concentration of 1 / 3 of the quantitative limit. The separation between adjacent peaks without interference near the target or between adjacent peaks and the target should be no less than 1.5. The test results are shown in Table 4.

[0060] Table 4

[0061]

[0062] 3. Specificity, as shown in Table 5

[0063] Table 5

[0064]

[0065]

[0066] 4. Limit of quantification, as shown in Table 6

[0067] Table 6

[0068]

[0069] As shown in Tables 3-6, the results of all verification indicators in this test met the requirements of the acceptance criteria.

Claims

1. A method for detecting 15 photoinitiators in an extract, characterized in that: The following steps are involved: S1, prepare 15 kinds of photoinitiator mixed standard working solutions, mobile phase, SST solution, blank solution and STD solution for use; S2, taking the extract, filtering it and preparing a blank extract for later use; S3, use ultra performance liquid chromatography-mass spectrometry to sample and analyze the extract, before sampling and analyzing the extract, first inject the mixed standard working solution and draw a standard curve, the order of injecting the extract includes: blank solution, SST solution, blank solution, STD solution, blank solution, blank extract, extract, blank solution, SST solution.

2. The method for detecting 15 photoinitiators in the extract according to claim 1, characterized in that: The mixed standard working solution, SST solution and STD solution all include acetonitrile.

3. The method for detecting 15 photoinitiators in the extract according to claim 2, characterized in that: The mobile phase includes a mobile phase A and a mobile phase B, wherein the mobile phase A includes a formic acid aqueous solution, and the mobile phase B includes methanol.

4. The method for detecting 15 photoinitiators in the extract according to claim 3, characterized in that: The concentration of the formic acid aqueous solution is 0.05-0.5 wt %.

5. The method for detecting 15 photoinitiators in the extract according to claim 4, characterized in that: The elution procedure of the liquid chromatography includes: 0-9 min, the content of mobile phase A in the mobile phase is 40-60 wt %, 9-12 min, the content of mobile phase A in the mobile phase is 1-5 wt %, and after 12 min, the content of mobile phase A in the mobile phase is 40-60 wt %.

6. The method for detecting 15 photoinitiators in the extract according to claim 1 or 5, characterized in that: The flow rate of the ultra-high performance liquid chromatography is 0.3-0.8 mL / min, the column temperature is 30-50° C., and the analysis time is 10-20 min.

7. The method for detecting 15 photoinitiators in the extract according to claim 6, characterized in that: The stationary phase of the chromatographic column used in the ultra-high performance liquid chromatography comprises C18; the inner diameter of the chromatographic column is 1-3 mm, the length is 50-150 mm, and the particle size of the stationary phase is 1-5 μm.

8. The method for detecting 15 photoinitiators in the extract according to claim 7, characterized in that: The mass spectrometer ionization method includes electrospray ionization, and the capillary positive ion voltage is 2-4 kV.

9. The method for detecting 15 photoinitiators in the extract according to claim 8, characterized in that: The sheath gas temperature of the mass spectrometer is 300-400° C., and the sheath gas flow rate is 10-15 L / min.

10. The method for detecting 15 photoinitiators in the extract according to claim 9, characterized in that: The nebulizer gas flow rate of the mass spectrometer is 5-10 L / min, and the nebulizer pressure is 40-50 psi.

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